The principal objective of this research is to develop improved methods for hyperpolarized helium-3 (3He) magnetic resonance imaging (MRI) of the lung. Hyperpolarized 3He was recently introduced as an inhaled contrast agent for MRI and has already shown substantial potential for providing medically relevant information about lung disease that is unmatched by any other modality. By exploiting the unique characteristics of hyperpolarized 3He, methods will be developed that improve the reproducibility of 3He MRI and permit a substantial increase in the acquisition speed or the signal-to-noise ratio compared to currently available strategies. Because the proposed techniques provide fundamental methodological improvements, they will be broadly applicable to 3He MRI of the lung, thereby substantially enhancing the potential for this exciting technology to strengthen our understanding of pulmonary function and pathology, and to improve our ability to diagnose and treat pulmonary diseases such as emphysema and asthma. Specifically, the research aims to: (1) develop a phase-based method for accurate transmitter calibration that can be integrated into a breath-hold image acquisition, eliminating the need for a separate dose of hyperpolarized gas to calibrate the scanner; (2) implement, optimize and evaluate new MRI pulse sequences that minimize signal loss due to the inherently high diffusivity of 3He, thereby limiting image blurring from this signal loss while permitting a substantially increased signal-to-noise ratio compared to current techniques; (3) evaluate the characteristics of 3He MRI of the lung over a range of magnetic field strengths as the basis for deriving field-strength optimized imaging configurations; and (4) implement a prototype multiple radio-frequency-coil array and evaluate the potential of parallel-acquisition methods to accelerate 3He MRI of the lung without a substantial loss in signal-to-noise ratio. The anticipated speed and signal-to-noise ratio improvements for 3He lung MRI that will result from success with these methods can be translated into important practical enhancements, such as increased spatial resolution, increased anatomical coverage in patients with impaired respiratory function, a decreased dose of hyperpolarized 3He while maintaining spatial resolution, or higher temporal resolution in dynamic functional studies. These advanced techniques will thereby provide a new quality of information and thus new opportunities for clinicians and scientists who endeavor to study and treat diseases of the lung.